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Sherrington used reflexes in the spinal cord as a way of investigating the general properties of neurons and the nervous system. These experiments led him to postulate "Sherrington's law of reciprocal innervation," which states that for every neural activation of a muscle, there is a corresponding inhibition of the opposing muscle. Sherrington is also known for his study of the synapse, a word which he coined for the then-theoretical connecting point of neurons. One of Sherrington's students, John Carew Eccles later won the Nobel Prize in 1963 for his work on the synapse. Other neuroscience research done by Sherrington investigated proprioception and the neural control of posture.

In addition to the nervous system, Sherrington studied a number of pressing medical issues of his time. In 1885 he went to Spain to investigate an outbreak of cholera. Sources differ as to whether Sherrington met Santiago Ramon y Cajal at this time. Although the official Nobel Prize biography of Sherrington mentions this meeting,[2] Sherringtion himself denied it in his euology of Cajal. Sherrington claimed the only meeting between them occurred when Cajal visited England, at Sherrington's invitation, to deliver the 1894 Croonian Lecture. Sherrington learned techniques in bacteriology and histology from Robert Koch while studying an outbreak of cholera in Berlin.